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Pharmacy > Science of Medicines Week 10 > Flashcards

Science of Medicines Week 10 Flashcards

1
Q

define bioavailability

A

a measure of the amount of drug that reaches its site of action AND the rate at which it gets there

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2
Q

define pharmacokinetics

A

what the body does to the drug

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3
Q

define pharmacodynamics

A

what the drug does to the body

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4
Q
A
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5
Q

define extravascular administration

A

not injecting into the blood e.g. tablet

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6
Q

What two steps does a drug need to achieve after administration to get into the systemic circulation?

A
  1. release
  2. absorption
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7
Q

define release

A

the drug dissolving at the administration site

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8
Q

define absorption

A

the drug crossing the biomembrane to reach the blood

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9
Q

What are the 2 steps of dissolution of a solid crystal in a liquid?

A
  1. solvation of the drug at the crystal surface to create a stagnant layer of saturated solution –> called the diffusion layer
  2. diffusion of the dissolved molecules across the diffusion layer into the bulk solution
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10
Q

Which equations gives the overall rate of dissolution at constant temperature?

A

Noyes-Whitney equation

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11
Q

Which 3 factors can be used to predict the solubility of a weakly acidic or basic drugs?

A

pH of solution, pKa, solubility of the unionised form (S0)

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12
Q

What are the 3 methods of membrane transport in the transcellular pathway?

A
  1. passive diffusion
  2. aqueous pore
  3. facilitated diffusion
  4. active transport
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13
Q

What is the equation used to calculate flux (diffusion)?

A

J= C x v x A

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14
Q

What does Fick’s 1st law describe?

A

rate of passive transport

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15
Q

What are the membrane properties affecting passive transport?

A

membrane thickness (h) and membrane area (A)

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16
Q

What are the drug properties affecting passive transport?

A

concentration gradient (C1-C2) and partition coefficient (K)

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17
Q

What are the drug and membrane properties affecting passive transport?

A

diffusivity (D)

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18
Q

What is used to give a drug’s lipophilicity?

A

LogP

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19
Q

drug that is 10x more lipid soluble than water soluble…

A

P=10
LogP=1

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20
Q

drug that is 100x more lipid soluble than water soluble…

A

P=100
LogP= 2

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21
Q

drug that is 5x more water soluble than lipid soluble…

A

P= 0.2
LogP= -0.7

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22
Q

What does Lipinski’s rule of 5 predict?

A

whether a drug will have good oral bioavailability

23
Q

What are Lipinski’s 5 rules?

A
  1. molecular weight is less than 500
  2. LogP is less than/equal to 5
  3. no more than 5 hydrogen bond donors
  4. no more than 10 hydrogen bond acceptors
  5. all units are multiples of 5
24
Q

define therapeutic window

A

the area of concentration of drug on a graph to have the efficacy needed

25
Q

Why is insulin administered by subcutaneous injection?

A

pepsin degrades polypeptides in the stomach, do cannot be administered orally

26
Q

What is the order of the rate of the stomach gradually releasing its contents into the small intestine?

A

zero order

27
Q

What is the order of the rate of the stomach gradually releasing its contents into the small intestine if in a fasted state?

A

first order

28
Q

What are 8 factors that affect gastric emptying and therefore drug absorption?

A
  1. meal volume
  2. type of meal
  3. physical state of stomach contents
  4. chemicals
  5. drugs
  6. body position
  7. disease
  8. exercise
29
Q

How does meal volume affect gastric emptying?

A

the larger the meal, the quicker the INITIAL gastric emptying

30
Q

How does the type of meal affect gastric emptying?

A

fatty acids, triglycerides, carbohydrates and amino acids all reduce gastric emptying rate

31
Q

How does physical state of stomach contents affect gastric emptying?

A

solutions or suspensions of small particles empty quicker than chunks of material

32
Q

How do chemicals affect gastric emptying?

A
  1. acids reduce emptying rate
  2. alkalis increase emptying rate at low concentrations and decrease it at higher concentrations
33
Q

How do drugs affect gastric emptying?

A

drugs including anticholinergics, narcotics, ethanol all reduce emptying rate

34
Q

How does body position affect gastric emptying?

A

lying on the left side reduces emptying rate

35
Q

How does disease affect gastric emptying?

A

emptying rate is reduced by the presence of ulcers and in some diabetics

36
Q

How does exercise affect gastric emptying?

A

vigorous exercise reduces emptying rate

37
Q

How does gastric emptying time affect drug absorption?

A

the longer the gastric emptying time, the longer it will take for the drug to appear in the systemic circulation

38
Q

What is one way membrane permeability can be increased?

A

using prodrugs

39
Q

How can using prodrugs increase membrane permeability?

A

can use a prodrug with high permeability, and after crossing the membrane, there are enzymes which convert the drug into its active form

40
Q

How may the stomach degrade drugs?

A

HCl= degrades some, so gastro-resistant coatings are needed
Pepsin= digestive protease destroys polypeptide drugs

41
Q

How may drugs be degraded in the duodenum?

A

Trypin, chymotrypsin, elastase, carboxypeptidase A and B degrade many large proteins

42
Q

How may drugs be degraded in the small intestine?

A

Cytochrome P450 enzymes
Esterases
Glucuronosyl transferases transfer glucuronic acid to nucleophilic sites on drugs

43
Q

How may drugs be degraded in the colon?

A

gut flora can metabolise and inactive drugs

44
Q

What is the hepatic first pass effect?

A
  1. drug passes intestinal membrane into systemic circulation
  2. drug is transport to liver via hepatic portal vein
  3. some drug is metabolised
  4. reduces bioavailability of the drug
45
Q

What are the 4 processes of transportation of drugs across the GI membrane?

A

paracellular transport, diffusion, facilitated diffusion, drug transporters

46
Q

define efflux pump

A

a cellular protein that can prevent intracellular accumulation of drug by pumping the drug that enters the cell immediately back out

47
Q

How can P-glycoprotein inhibitors help with cancer treatment?

A
  1. P-glycoprotein is an efflux pump that prevents chemotherapeutic drugs entering cancerous cells
  2. also prevents oral delivery due to presence in intestinal epithelial cells
  3. co-administration prevents drug efflux
48
Q

What are the 4 types of absorption rates for oral dosage forms?

A
  1. rapid release
  2. delayed release
  3. slow release (zero order kinetics)
  4. slow release (1st order kinetics)
49
Q

What is Cmax and Tmax?

A

Cmax = maximum concentration in serum
Tmax = time taken to reach maximum concentration (Cmax)

50
Q

What are the characteristics of delayed absorption on a graph?

A

delayed and fast absorption have the same Cmax values but different Tmax due to a large lag time

51
Q

What does the amount of a first order absorption drug absorbed per unit depend on?

A

concentration of drug at the site of absorption -> the greater the amount to be absorbed the faster the absorption rate

52
Q

Is drug absorption for zero order absorption dependent on quantity of drug at site of absorption?

A

no, the amount released per unit time is constant, for example by a particular tablet coating method

53
Q

How must tetracyclines be taken?

A

on fasted stomach as GI absorption is decreased by Al, Ca, Mg and Fe presence (also milk products!)

54
Q

What can’t you take antacids with?

A

milk products as the calcium can react with them and prevent them being absorbed

Pharmacy (15 decks)

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